Novel PET/CT Imaging Biomarkers of CB-839 in Combination With Panitumumab and Irinotecan in Patients With Metastatic and Refractory RAS Wildtype Colorectal Cancer

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Objectives: Primary Objective of Phase I: • Determine the maximum tolerated dose (MTD) of CB839 in combination with panitumumab and irinotecan Primary Objective of Phase II: • Determine the efficacy of CB-839 in combination with panitumumab as measured by the objective response rate (RR) in patients...

Objectives: Primary Objective of Phase I: • Determine the maximum tolerated dose (MTD) of CB839 in combination with panitumumab and irinotecan Primary Objective of Phase II: • Determine the efficacy of CB-839 in combination with panitumumab as measured by the objective response rate (RR) in patients with previously EGFR treated RAS wildtype colorectal adenocarcinoma. Secondary Objectives of Phase II: Determine the disease control rate, progression-free survival, and overall survival (phase II). Correlate radiological features of pre- and post-treatment carbon C 11 glutamine (11C-glutamine) positron emission tomography (PET)/computed tomography (CT) and fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) PET/CT with clinical outcome and biological correlates (tissue gene signature, plasma glutamate levels, exosomes). (Phase II). Collect pre-treatment biopsy tissue and prospectively correlate clinical outcome with a glutamate-biased gene set. (Phase II) Quantify exosomal content in the plasma (Phase II). Collect blood samples during each radiotracer injection to assess pharmacokinetics EXPLORATORY OBJECTIVES: Correlate radiological features of pre- and post-treatment 11C-Glutamine PET/CT and 18F-FSPG PET/CT with clinical outcome. (Phase I) Correlate radiological features of pre- and post-treatment 11C-Acetate PET/CT with clinical outcome (Phase II). OUTLINE: Phase I is a dose-escalation study of glutaminase inhibitor CB-839 in combination with standard doses of panitumumab and irinotecan hydrochloride. Phase II will study efficacy of glutaminase inhibitor CB-839 in combination with standard doses of panitumumab. Patients receive glutaminase inhibitor CB-839 orally (PO) twice daily (BID) on days 1-28, panitumumab intravenously (IV) over 60-90 minutes on days 1 and 15, and irinotecan hydrochloride IV over 90 minutes on day 1 and 15 (Phase I only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 28 days and then every 3 months for up to 1 year.

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